Dopamine D3 Receptor Mutant Mice Exhibit Increased Behavioral Sensitivity to Concurrent Stimulation of D1 and D2 Receptors

The dopamine D3 receptor is expressed primarily in regions of the brain that are thought to influence motivation and motor functions. To specify in vivo D3 receptor function, we generated mutant mice lacking this receptor. Our analysis indicates that in a novel environment, D3 mutant mice are transi...

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Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 1997-10, Vol.19 (4), p.837-848
Main Authors: Xu, Ming, Koeltzow, Timothy E, Santiago, Giovanni Tirado, Moratalla, Rosario, Cooper, Donald C, Hu, Xiu-Ti, White, Norman M, Graybiel, Ann M, White, Francis J, Tonegawa, Susumu
Format: Article
Language:English
Subjects:
Amphetamine - pharmacology
Animals
Anxiety
Chimera
Cocaine - pharmacology
Conditioning, Operant
Crosses, Genetic
Cues
Dopamine Agonists - pharmacology
Electrophysiology - methods
Female
Habituation, Psychophysiologic
Male
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Mice, Knockout
Motor Activity - drug effects
Motor Activity - physiology
Neurons - drug effects
Neurons - physiology
Nucleus Accumbens - drug effects
Nucleus Accumbens - physiology
Polymerase Chain Reaction
Receptors, Dopamine D1 - physiology
Receptors, Dopamine D2 - deficiency
Receptors, Dopamine D2 - genetics
Receptors, Dopamine D2 - physiology
Receptors, Dopamine D3
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Summary:The dopamine D3 receptor is expressed primarily in regions of the brain that are thought to influence motivation and motor functions. To specify in vivo D3 receptor function, we generated mutant mice lacking this receptor. Our analysis indicates that in a novel environment, D3 mutant mice are transiently more active than wild-type mice, an effect not associated with anxiety state. Moreover, D3 mutant mice exhibit enhanced behavioral sensitivity to combined injections of D1 and D2 class receptor agonists, cocaine and amphetamine. However, the combined electrophysiological effects of the same D1 and D2 agonists on single neurons within the nucleus accumbens were not altered by the D3 receptor mutation. We conclude that one function of the D3 receptor is to modulate behaviors by inhibiting the cooperative effects of postsynaptic D1 and other D2 class receptors at systems level.
ISSN:0896-6273
1097-4199
DOI:10.1016/S0896-6273(00)80965-4